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Medicine Nobel for research on how cells 'eat themselves'

October 3, 2016 This article courtesy of Nature News.

Japanese biologist Yoshinori Ohsumi recognized for work on autophagy.

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Molecular biologist Yoshinori Ohsumi has won the 2016 Nobel Prize in Physiology or Medicine for his work in the field of autophagy: the processes by which the cell digests and recycles its own components.

The 71-year-old Ohsumi, who is currently a professor at the Tokyo Institute of Technology in Yokohama, was recognized for his experiments in the 1990s, when he used baker's yeast (Saccharomyces cerevisiae) to identify genes that control how cells destroy their own contents. The same kinds of mechanism operate in human cells — and are sometimes involved in genetic disease.

"He's a very humble yeast geneticist who basically transformed the field," says Sharon Tooze, a cell biologist at the Francis Crick Institute in London. "He was interested in this weird pathway that turns out to be a vitally important pathway in medicine."

The word 'autophagy' — from the Greek for 'self-eating' — was coined in 1963 by the Belgian biochemist Christian de Duve, who saw how cells broke down their parts inside a waste-processing sac that he called a lysosome. Biologists now understand that this process is fundamentally important to living cells.

"Without autophagy our cells won't survive," says Juleen Zierath, a physiologist at the Karolinska Institute in Stockholm who was on the selection committee for the medicine Nobel. When cells are starved, they can consume their own proteins for fuel. The same degradation process can be used to eliminate damaged proteins and organelles — effectively, to renew cells and clear out debris — or to ward off invading bacteria and viruses.

Sleepy backwater

Ohsumi began studying yeast as a postdoc, turning to yeast DNA replication as a side project when his main research stalled, says Tooze. When Ohsumi first started studying autophagy in 1988, “it was kind of a sleepy backwater of a research topic,” says biochemist Michael Hall of the University of Basel in Switzerland. “It was basically considered the garbage-disposal system of the cell — just bulk, non-specific degradation of junk.”

In an interview given to the Tokyo Institute of Technology's website in December 2012, Ohsumi said that all his research findings began with a love of the microscope. "You can answer the most basic and important questions about the nature of life through yeasts," he added.

Ohsumi would go on to develop the first yeast genetics screen to identify genes involved in the autophagy pathway. But it was a few years before biologists recognized the importance of the process in physiology and disease.

Interest in the field skyrocketed when, in 1999, Beth Levine (now at the University of Texas Southwestern Medical Center in Dallas) and her colleagues reported that a mammalian autophagy gene could suppress tumour growth. That finding launched widespread efforts to learn more about the role of autophagy in cancer.

Disruptions in autophagy have also been linked to Parkinson's disease, type 2 diabetes and other disorders — and research is ongoing to develop drugs that can affect the process.

Researchers’ understanding of the complex role of autophagy in cancer has become more detailed: the process seems to inhibit tumours in the early stages of their growth, but can also fuel cancer once it has spread, says Hall.

Single winner

Ohsumi, who will collect 8 million Swedish kronor (US$940,000) for the Nobel prize, also won the ¥50-million (US$626,000) Kyoto Prize in basic sciences in 2012 for his autophagy work.

Others have made key contributions to the field, and were considered to be contenders for a share of a Nobel. Biochemist Michael Thumm of the University Medical Center Göttingen in Germany, for example, also discovered autophagy genes, as did cell biologist Daniel Klionsky of the University of Michigan in Ann Arbor.

“If they’re going to give it to just one, Ohsumi’s the one,” says Hall. “But it also would have been good to include other people.”

In Japan, the prize had been widely anticipated for the past few years, with journalists showing up regularly to ask Ohsumi for interviews, says Hitoshi Nakatogawa, a biologist at the Tokyo Institute of Technology who has worked with Ohsumi for a decade. When colleagues heard — around two hours before the official announcement — of Ohsumi’s win, they gathered together to celebrate in the victor’s lab. “We talked about how great it was that he won it alone,” he says.

“Ohsumi never overlooks anything even in the most banal kind of experiment,” Nakatogawa adds. “He doesn't care about whether it will lead to something useful, whether a breakthrough can be expected, whether it will lead to more funding. He just follows his curiosity.”

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